Reinforced Supramolecular Hydrogels from Attapulgite and Cyclodextrin Pseudopolyrotaxane for Sustained Intra-Articular Drug Delivery

Macromol Biosci. 2021 Jan;21(1):e2000299. doi: 10.1002/mabi.202000299. Epub 2020 Oct 11.

Abstract

Injectable hydrogels for nonsteroidal anti-inflammatory drugs' (NSAIDs) delivery to minimize the side effects of NSAIDs and achieve long-term sustained release at the targeted site of synovial joint are attractive for osteoarthritis therapy, but how to improve its mechanical strength remains a challenge. In this work, a kind of 1D natural clay mineral material, attapulgite (ATP), is introduced to a classical cyclodextrin pseudopolyrotaxane (PPR) system to form a reinforced supramolecular hydrogel for sustained release of diclofenac sodium (DS) due to its rigid, rod-like morphology, and unique structure, which has great potential in tissue regeneration, repair, and engineering. Investigation on the interior morphology and rheological property of the obtained hydrogel points out that the ATP distributed in PPR hydrogel plays a role similar to the "reinforcement in concrete" and exhibits a positive effect on improving the mechanical properties of PPR hydrogel by regulating their interior morphology from a randomly distributed style to the well-ordered porous frame structure. The hybrid hydrogels demonstrate good shear-thinning and thixotropic properties, excellent biocompability, and sustained release behavior both in vitro and in vivo. Furthermore, preliminary in vivo treatment in an acute inflammatory rat model reveals that the ATP hybrid hydrogels present sustained anti-inflammatory effect.

Keywords: attapulgite; injectable; intra-articular drug delivery; supramolecular hydrogel; sustained release.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Bone Regeneration / drug effects*
  • Cyclodextrins / pharmacology
  • Diclofenac / pharmacology
  • Disease Models, Animal
  • Drug Delivery Systems
  • Drug Liberation / drug effects
  • Humans
  • Hydrogels / chemistry
  • Hydrogels / pharmacology*
  • Injections, Intra-Articular
  • Magnesium Compounds / pharmacology*
  • Osteoarthritis / drug therapy*
  • Osteoarthritis / pathology
  • Poloxamer / pharmacology
  • Polyethylene Glycols / pharmacology
  • Rats
  • Rotaxanes / pharmacology
  • Silicon Compounds / pharmacology*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclodextrins
  • Hydrogels
  • Magnesium Compounds
  • Rotaxanes
  • Silicon Compounds
  • pseudopolyrotaxane
  • Poloxamer
  • Diclofenac
  • Polyethylene Glycols
  • attapulgite